Compounds, their preparation and use

Abstract

The present invention relates to compounds of the general formula (I)The compounds are useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).

What is claimed is:  
     
       1. A compound of formula (I)                    
       wherein 
       ring A and ring B, fused to the ring containing X and T, independently of each other represents a phenyl ring, optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro, cyano, formyl, or C 1-12 -alkyl, C 4-12 -alkenynyl, C 2-12 -alkenyl, C 2-12 -alkynyl, C 1-12 -alkoxy, aryloxy, arylalkyl, arylalkoxy, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy, acyl, acyloxy, hydroxyC 1-12 -alkyl, amino, acylamino, C 1-12 -alkyl-amino, arylamino, arylalkylamino, amino-C 1-12 -alkyl, C 1-12 -alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, C 1-12 -alkoxyC- 1-12 -alkyl, aryloxyC 1-12 -alkyl, arylalkoxyC 1-12 -alkyl, C 1-12 -alkylthio, thioC 1-12 -alkyl, C 1-12 -alkoxycarbonylamino, aryloxycarbonylamino, arylalkoxycarbonylamino, bicycloalkyl, (C 3-6 -cycloalkyl)C 1-6 -alkyl, C 1-6 -dialkylamino, C 1-6 -alkylsulfonyl, C 1-6 -monoalkylaminosulfonyl, C 1-6 -dialkylaminosulfonyl, arylthio, arylsulfonyl, C 1-6 -monoalkylaminocarbonyl, C 1-6 -dialkylaminocarbonyl, —COR 6  or —SO 2 R 7 , wherein R 6  and R 7  independently of each other are selected from hydroxy, halogen, perhalomethyl, C 1-6 -alkoxy or amino optionally substituted with one or more C 1-6 -alkyl or perhalomethyl;  
       X is —O—;  
       T is N;  
       k is 2;  
       Ar represents arylene, heteroarylene, or a divalent heterocyclic group each of which can optionally be substituted with one or more halogen,C 1-6 -alkyl, amino, hydroxy, C 1-6 -alkoxy or aryl;  
       R 1  represents hydrogen, hydroxy, halogen, C 1-12 -alkoxy, C- 1-12 -alkyl, C 4-12 -alkenynyl, C 2-12 -alkenyl, C 2-12 -alkynyl or arylalkyl; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano;  
       R 2  represents hydrogen, hydroxy, halogen, C 1-12 -alkoxy, C 1-2 -alkyl, C 4-12 -alkenynyl, C 1-2 -alkenyl, C 2-12 -alkynyl or arylalkyl; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano; or R 2  forms a bond together with R 3 ;  
       R 3  represents hydrogen, hydroxy, halogen, C 1-12 -alkoxy, C 1-12 -alkyl, C 4-12 -alkenynyl, C 2-12  -alkenyl, C 2-12 -alkynyl, acyl or arylalkyl; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano; or R 3  forms a bond together with R 2 ;  
       R 4  represents hydrogen, C 1-12 -alkyl, C 4-12 -alkenynyl, C 2-12 -alkenyl, C 2-12 -alkynyl, aryl, arylalkyl heterocyclyl, heteroaryl or heteroarylalkyl groups; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano;  
       R 5  represents hydrogen, C 1-12 -alkyl, C 4-12 -alkenynyl, C 2-12 -alkenyl, C 2-12 -alkynyl, aryl, arylakyl, heterocyclyl, heteroaryl or heteroarylalkyl groups; optionally substituted with one or more halogen, perhalomethyl, hydroxy, nitro or cyano;  
       Z represents oxygen or NR 12 , wherein R 12  represents hydrogen C 1-12 -alkyl, aryl, hydroxyC 1-12  -alkyl or arylalkyl groups or when Z is NR 12 , R 4  and R 12  may form a 5 or 6 membered nitrogen containing ring, optionally substituted with one or more C 1-6 -alkyl;  
       Q represents oxygen or NR 13 , wherein R 13  represents hydrogen C 1-12 -alkyl, aryl, hydroxyC 1-12 -alkyl or arylalkyl groups or when Q is NR 3 , R 5  and R 13  may form a 5 or 6 membered nitrogen containing ring, optionally substituted with one or more C 1-6 -alkyl;  
       n is an integer ranging from 0 to 3;  
       m is an integer ranging from 0 to 1;  
       or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, or any tautomeric forms. 
     
     
       2. The compound of  claim 1  wherein ring A and ring B, fused to the ring containing X and T independently of each other represents a phenyl ring, optionally substituted with halogen, C 1-6 -alkyl or aryl, wherein the aryl can be substituted with one or more halogen or C 1-6 -alkyl. 
     
     
       3. The compound of  claim 1  wherein ring A and ring B, fused to the ring containing X and T independently of each other represents a phenyl ring. 
     
     
       4. The compound of  claim 1  wherein Ar represents arylene. 
     
     
       5. The compound of  claim 1  wherein R 1 , R 2  and R 3  represents hydrogen. 
     
     
       6. The compound of  claim 1  wherein R 4  and R 5  represents hydrogen or methyl. 
     
     
       7. The compound of  claim 1  wherein Z and Q represents O. 
     
     
       8. The compound of  claim 1  wherein n is 1. 
     
     
       9. The compound of  claim 1  wherein m is 1. 
     
     
       10. The compound of  claim 1  comprising 
       2-{4-(2-Phenoxazine-10-yl-ethoxy)-benzyl]-malonic acid dimethyl ester,  
       2-{4-(2-Phenoxazine-10-yl-ethoxy)-benzyl]-malonic acid;  
       or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, or any tautomeric forms. 
     
     
       11. A pharmaceutical composition comprising, as an active ingredient, the compound of  claim 1 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent. 
     
     
       12. The composition of  claim 11  in unit dosage form, comprising from 0.05 to 100 mg of the compound or a pharmaceutically acceptable salt thereof. 
     
     
       13. A method for the treatment of diabetes and/or obesity, the method comprising administering to a subject in need thereof an effective amount of the compound of  claim 1 . 
     
     
       14. The compound of  claim 1 , wherein the mixture of optical isomers is a racemic mixture. 
     
     
       15. The compound of  claim 10 , wherein the mixture of optical isomers is a racemic mixture. 
     
     
       16. The composition of  claim 12 , comprising from 0.1 to 50 mg of the compound or a pharmaceutically acceptable salt thereof.